Grignard Reactions

Introduction

• Developed: 1912, Nobel Prize-winning
• Importance: Essential for forming new carbon-carbon bonds
• Conditions: Anhydrous environments (e.g., diethyl ether)

Basic Concept

• Starting Material: Alkyl halide (e.g., alkyl bromide)
• Reaction with Magnesium:
  • Magnesium inserts into the carbon-halogen bond
  • Creates a compound with carbon bonded to magnesium and halogen (e.g., C-Mg-Br)
  • Inverts the polarity of carbon (carbon becomes partially negative, magnesium partially positive)

Grignard Reagents

• Definition: Alkyl halide with magnesium inserted (e.g., C-Mg-Br)
• Nucleophilic Carbon: Uncommon source of nucleophilic carbon due to its electron excess
• Reaction with Carbonyl Compounds:
  • Target Compounds: Aldehydes, ketones
  • Mechanism:
    1. Nucleophilic carbon attacks carbonyl carbon
    2. Forms an oxyanion
    3. Protonation in acidic workup produces alcohol

Example Reactions

• Aldehyde Reaction:
  • 3-carbon Grignard reagent + 2-carbon aldehyde → 5-carbon alcohol
  • New carbon-carbon bond formed
• Ketone Reaction:
  • Methyl Grignard reagent + ketone → alcohol
  • Similar mechanism as aldehyde reaction
• Ester Reaction:
  • Methyl Grignard reagent + ester → intermediate with new carbonyl
  • Can add another equivalent of Grignard reagent
  • Produces larger molecules

Important Considerations

• Strictly Anhydrous Conditions:
  • No water can be present (even atmospheric moisture can destroy the Grignard reagent)
  • Example of destruction: R-Mg-Br + H₂O → R-H + unusable byproduct
• Solvents: Typically diethyl ether or other anhydrous solvents

Specific Notes

• Reactions with Carboxylic Acids: Generally not reactive
• Reactions with Esters: Can allow addition of two Grignard reagents, forming larger molecules

Conclusion

• Summary: Grignard reactions are powerful for building larger organic molecules by forming new carbon-carbon bonds
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